UMass Chan, University of Queensland researchers discover genomic immunity to koala retrovirus

New research into how a retrovirus is spreading across populations of wild koalas in Queensland, Australia is leading to a better understanding of the evolution of the animal’s genome. 

Published this month in the journal Cell by scientists at UMass Chan Medical School and the University of Queensland, the paper explains how the animals adapted genomic immunity to the koala retrovirus  (KoRV-A), by shutting it down, or silencing it, as it becomes a component of the genome. This is important because most wild koalas are born with this pathogen as part of their genetic material.   

KoRV-A is spreading between wild koalas by infecting germ cells that make eggs and sperm, suppressing the immune system and making the animals susceptible to cancer and secondary chlamydia infection.  

Scientists report that a copy of the virus is captured by a host gene, and the germ cells process the product of this modified gene into small pieces of “anti-KoRV-A” RNA, known as piRNAs.  The virus sequences captured in piRNAs are used to find copies of the pathogen in the genome, turning them off.   

“The virus first infected koalas in the northern part of Australia and is spreading to the south while infecting germ cells and becoming a component of the genome. The north to south spread allowed us to watch how germ cells learn to control a brand-new infection,” said William E. Theurkauf, PhD, professor of molecular medicine at UMass Chan. 

The UMass Chan team includes Zhiping Weng, PhD, the Li Weibo Chair in Biomedical Research and professor of genomics and computational biology; Jeremy Luban, MD, the David J. Freelander Memorial Professor in AIDS Research and professor of molecular medicine; Tianxiong Yu, PhD, a postdoctoral associate working in Dr. Weng’s lab.  

Retroviruses can lead to serious illnesses and have also played a notable role in shaping human evolution. Through millions of years of human evolution, retroviruses have influenced developmental processes. Genes derived from retroviruses have been “highjacked” for placental development and information storage in the brain. Weng underscored the significance of the viral invasion in wild koalas in understanding genome evolution and its broader implications for other mammalian genomes. 

“For mammals, the most recent viral invasion of the germline was millions of years ago. This invasion is estimated to be in the 5,000-year range and is still in progress. Discovering how this virus is controlled reveals how viruses modified other mammalian genomes,” Weng said. 

The UMass Chan team is collaborating with Keith Chappell, PhD, professor at the University of Queensland; postdoctoral fellow Michaela Blyton, PhD; and their team. Dr. Chappell highlighted the unique opportunity presented by the koala population. 

“Out of all the species on the planet, the koala is the only one where we can see a genetic response to a retrovirus in real time,” Dr. Chappell said. “This allows the researchers to study exactly how these iconic critters are responding. It’s a pretty amazing situation.”